CN109265488A - Iridium anticancer complex and its preparation method and application containing two tooth cheland of phosphinimine - Google Patents
Iridium anticancer complex and its preparation method and application containing two tooth cheland of phosphinimine Download PDFInfo
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- CN109265488A CN109265488A CN201811344740.1A CN201811344740A CN109265488A CN 109265488 A CN109265488 A CN 109265488A CN 201811344740 A CN201811344740 A CN 201811344740A CN 109265488 A CN109265488 A CN 109265488A
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- diphenylphosphanyl
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- GKOZUEZYRPOHIO-UHFFFAOYSA-N iridium atom Chemical compound [Ir] GKOZUEZYRPOHIO-UHFFFAOYSA-N 0.000 title claims abstract description 30
- 230000001093 anti-cancer Effects 0.000 title claims abstract description 25
- 229910052741 iridium Inorganic materials 0.000 title claims abstract description 23
- QLNAVQRIWDRPHA-UHFFFAOYSA-N iminophosphane Chemical compound P=N QLNAVQRIWDRPHA-UHFFFAOYSA-N 0.000 title claims abstract description 13
- 238000002360 preparation method Methods 0.000 title claims abstract description 12
- 229910052751 metal Inorganic materials 0.000 claims abstract description 9
- 239000002184 metal Substances 0.000 claims abstract description 9
- 125000001424 substituent group Chemical group 0.000 claims abstract description 7
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 37
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 claims description 30
- 239000007787 solid Substances 0.000 claims description 25
- 238000003756 stirring Methods 0.000 claims description 25
- 229910021135 KPF6 Inorganic materials 0.000 claims description 24
- 239000003153 chemical reaction reagent Substances 0.000 claims description 24
- 238000009792 diffusion process Methods 0.000 claims description 24
- 239000012265 solid product Substances 0.000 claims description 24
- 239000002904 solvent Substances 0.000 claims description 19
- 150000002503 iridium Chemical class 0.000 claims description 18
- 239000000460 chlorine Substances 0.000 claims description 17
- 239000003446 ligand Substances 0.000 claims description 11
- 229910052739 hydrogen Inorganic materials 0.000 claims description 10
- 239000001257 hydrogen Substances 0.000 claims description 10
- 238000001953 recrystallisation Methods 0.000 claims description 8
- 125000003118 aryl group Chemical group 0.000 claims description 7
- 239000003814 drug Substances 0.000 claims description 6
- 239000003795 chemical substances by application Substances 0.000 claims description 5
- 150000001875 compounds Chemical group 0.000 claims description 5
- 125000000217 alkyl group Chemical group 0.000 claims description 4
- 238000000034 method Methods 0.000 claims description 4
- 229910017717 NH4X Inorganic materials 0.000 claims description 2
- 238000006243 chemical reaction Methods 0.000 claims description 2
- 229910052801 chlorine Inorganic materials 0.000 claims description 2
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 2
- 125000002897 diene group Chemical group 0.000 claims description 2
- 229910052736 halogen Inorganic materials 0.000 claims description 2
- 150000002367 halogens Chemical class 0.000 claims description 2
- 238000006467 substitution reaction Methods 0.000 claims description 2
- -1 methyl (diphenylphosphanyl) phenyl Chemical group 0.000 claims 8
- WDWDWGRYHDPSDS-UHFFFAOYSA-N methanimine Chemical compound N=C WDWDWGRYHDPSDS-UHFFFAOYSA-N 0.000 claims 3
- 239000003560 cancer drug Substances 0.000 claims 1
- 229940079593 drug Drugs 0.000 claims 1
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims 1
- 239000002246 antineoplastic agent Substances 0.000 abstract description 8
- 206010028980 Neoplasm Diseases 0.000 abstract description 7
- 229940041181 antineoplastic drug Drugs 0.000 abstract description 7
- 201000011510 cancer Diseases 0.000 abstract description 6
- 238000012986 modification Methods 0.000 abstract description 6
- 230000004048 modification Effects 0.000 abstract description 6
- 239000000758 substrate Substances 0.000 abstract description 5
- 210000002919 epithelial cell Anatomy 0.000 abstract description 4
- 210000004907 gland Anatomy 0.000 abstract description 4
- 230000012010 growth Effects 0.000 abstract description 2
- 238000000338 in vitro Methods 0.000 abstract description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 36
- 238000001228 spectrum Methods 0.000 description 17
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 12
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 12
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Substances [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 11
- 229910052698 phosphorus Inorganic materials 0.000 description 9
- 239000011574 phosphorus Substances 0.000 description 9
- 238000005160 1H NMR spectroscopy Methods 0.000 description 8
- 238000004679 31P NMR spectroscopy Methods 0.000 description 8
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 8
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 8
- 238000001819 mass spectrum Methods 0.000 description 8
- 238000001840 matrix-assisted laser desorption--ionisation time-of-flight mass spectrometry Methods 0.000 description 8
- 229910052697 platinum Inorganic materials 0.000 description 7
- 230000000694 effects Effects 0.000 description 6
- 239000000126 substance Substances 0.000 description 5
- KWBVHRQKJDZOLZ-UHFFFAOYSA-N 1-(2-diphenylphosphanylphenyl)-n-(2-phenylethyl)methanimine Chemical compound C=1C=CC=C(P(C=2C=CC=CC=2)C=2C=CC=CC=2)C=1C=NCCC1=CC=CC=C1 KWBVHRQKJDZOLZ-UHFFFAOYSA-N 0.000 description 4
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 4
- CWYDMJZWNROFGL-UHFFFAOYSA-N n-cyclohexyl-1-(2-diphenylphosphanylphenyl)methanimine Chemical compound C1CCCCC1N=CC1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 CWYDMJZWNROFGL-UHFFFAOYSA-N 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- 206010059866 Drug resistance Diseases 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- URWYPOVFVSLUFZ-UHFFFAOYSA-N 1-(2-diphenylphosphanylphenyl)-n-[2,6-di(propan-2-yl)phenyl]methanimine Chemical compound CC(C)C1=CC=CC(C(C)C)=C1N=CC1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 URWYPOVFVSLUFZ-UHFFFAOYSA-N 0.000 description 2
- DCVKIYDNMMCCBG-UHFFFAOYSA-N 1-(2-diphenylphosphanylphenyl)-n-phenylmethanimine Chemical compound C=1C=CC=C(P(C=2C=CC=CC=2)C=2C=CC=CC=2)C=1C=NC1=CC=CC=C1 DCVKIYDNMMCCBG-UHFFFAOYSA-N 0.000 description 2
- FQMPKTVMWAMEJX-UHFFFAOYSA-N N-(2,6-dimethylphenyl)-1-(2-diphenylphosphanylphenyl)methanimine Chemical compound C1(=CC=CC=C1)P(C1=C(C=NC2=C(C=CC=C2C)C)C=CC=C1)C1=CC=CC=C1 FQMPKTVMWAMEJX-UHFFFAOYSA-N 0.000 description 2
- 150000004696 coordination complex Chemical class 0.000 description 2
- 150000002466 imines Chemical class 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- QBOUGYKYLUGQJN-UHFFFAOYSA-N n-benzyl-1-(2-diphenylphosphanylphenyl)methanimine Chemical compound C=1C=CC=CC=1CN=CC1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 QBOUGYKYLUGQJN-UHFFFAOYSA-N 0.000 description 2
- 229910000073 phosphorus hydride Inorganic materials 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 239000011550 stock solution Substances 0.000 description 2
- 231100000331 toxic Toxicity 0.000 description 2
- 230000002588 toxic effect Effects 0.000 description 2
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 239000006285 cell suspension Substances 0.000 description 1
- 239000013522 chelant Substances 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 description 1
- 229960004316 cisplatin Drugs 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 210000004748 cultured cell Anatomy 0.000 description 1
- 125000000753 cycloalkyl group Chemical group 0.000 description 1
- 125000000058 cyclopentadienyl group Chemical group C1(=CC=CC1)* 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- RAABOESOVLLHRU-UHFFFAOYSA-N diazene Chemical compound N=N RAABOESOVLLHRU-UHFFFAOYSA-N 0.000 description 1
- 229910000071 diazene Inorganic materials 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 1
- 239000010931 gold Substances 0.000 description 1
- 229910052737 gold Inorganic materials 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 150000002431 hydrogen Chemical class 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 229910021432 inorganic complex Inorganic materials 0.000 description 1
- 231100001231 less toxic Toxicity 0.000 description 1
- 239000003863 metallic catalyst Substances 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- 238000006053 organic reaction Methods 0.000 description 1
- WQIQNKQYEUMPBM-UHFFFAOYSA-N pentamethylcyclopentadiene Chemical compound CC1C(C)=C(C)C(C)=C1C WQIQNKQYEUMPBM-UHFFFAOYSA-N 0.000 description 1
- 125000004437 phosphorous atom Chemical group 0.000 description 1
- 239000002574 poison Substances 0.000 description 1
- 231100000614 poison Toxicity 0.000 description 1
- 238000006116 polymerization reaction Methods 0.000 description 1
- 230000001376 precipitating effect Effects 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F17/00—Metallocenes
- C07F17/02—Metallocenes of metals of Groups 8, 9 or 10 of the Periodic System
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/07—Optical isomers
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
Abstract
The invention discloses a kind of organic metal iridium anticancer complex containing two tooth cheland of phosphinimine,；Preparation method is also disclosed, the complex of preparation is inhibited to the growth of gland cancer mankind's alveolar substrate epithelial cell (A549), illustrates it with good Anticancer Activity in vitro.Complex of iridium in the present invention can carry out the modification of substituent group in multiple positions, and anticancer activity is good, is the potential anticancer drug of new class.
Description
Technical field
The present invention relates to metal complex, specially a kind of iridium anticancer complex containing two tooth cheland of phosphinimine and
Preparation method and application, belong to chemical pharmacy field.
Background technique
Cancer has become one of the difficult medical problem that the mankind urgently capture.Chemotherapy is the main plan of current treating cancer
Slightly.The first kind is applied to the representative cis-platinum (PtCl of clinical Metal Substrate anticancer drug2(NH3)2, cisplatin) and due to its poison
Side effect is big, is also easy to produce drug resistance and invalid to some oncotherapies, limits its further clinical use.Therefore it finds
Efficiently, less toxic, the anticancer drug of wide spectrum becomes the hot spot of the area researches such as chemistry, biology and medicine.Although a new generation closes
At divalent platinum complex reduce some toxic side effects, but toxic side effect still has, and drug resistance problems remain on presence.I
It is expected in terms for the treatment of tumour chemically therapy obtain preferably development, this just need to continue research have different role mechanism
Novel metal anticancer drug, to improve or supplement the performance of existing platinum medicine.Among these compounds, organic metal cooperates
Object has filled up the blank between traditional inorganic complexes anticancer drug and organic anticancer drug because its structure is easily modified, and shows
Higher activity and anti-drug resistance out.Wherein, the half sandwich-type hexa-coordinate iridium organometallic complex containing cyclopentadienyl group because
The diversity of its structure and different from platinum medicine anticancer mechanism and be concerned.Currently, researcher has synthesized two
The pentamethylcyclopentadiene base Ir of imine ligand and bidentate phosphine ligandsIIIOrganometallic complex, (Inorg. Chem, 2018, 57 (11) :6669-6685)、(Inorg. Chem, 2018,57 (4): 1705-1716), it shows preferable antitumor
Activity and have different from platinum medicine multiple anticancer mechanism.
Phosphinimine (P^N) ligand is chiefly used in synthesizing metallic catalyst simultaneously as the significant unsymmetric ligand of a trans-effect
Applied to catalysis organic reaction and polymerization.Relative to diimide ligand and bidentate phosphine ligands, the coordination center atom of the ligand
It is an electronics unsymmetric structure, phosphorus atoms are very strong σ-electron donor, being capable of stable metal；And the nitrogen-atoms in imines
Coordination ability it is relatively weak, changeability can be provided for the chemical and biological activity of complex.
Summary of the invention
To solve the above-mentioned problems, the neutral ligand that the present invention selects P^N to chelate as two teeth synthesizes a kind of novel
With high anti-cancer activity complex of iridium, the potential anticancer drug of new class is promised to be.
The present invention is achieved by the following technical solutions:
A kind of iridium anticancer complex containing two tooth cheland of phosphinimine, the organic metal complex of iridium are phosphorus nitrogen-atoms and gold
Belong to the complex of iridium coordination, and there is anticancer activity, structural formula is as shown in the formula (I):
；
In formula (I), R1For hydrogen, aryl, alkyl, naphthenic base, halogen；R2、R3It is independently of one another naphthenic base or C7~C30Substitution
Aryl；R4For C1~C15Alkyl or C6~C30Aryl；X is Cl-、PF6 -、BF4 -、BPh4 -、SbF6 -、。
Preferably, the R1Aryl on substituent group be C1~C12Alkyl.
Aryl, alkyl, naphthenic base may be halogenated alkyl, halogenated cycloalkyl, halogenated aryl.
Formula (I) particular compound structure provided by the invention are as follows:
。
The preparation method of organic metal iridium anticancer complex of the present invention, using following steps:
；
Reaction forms the ring penta containing substituent group under the conditions of iridium dimer, two tooth ligand of P^N and AX are added in methylene chloride
The hexa-coordinate complex of iridium of diene ring, two tooth cheland of P^N and chlorine atom and metal iridium coordination；The AX be NaX,
KX, AgX or NH4X。
The synthetic method specific steps of eight complex 1-8 are as follows:
(1) by 39.8 mg iridium dimer (R1For methyl), 1- (2- (diphenylphosphanyl) phenyl)-N-
Phenylmethanimine (36.5mg, 0.10 mmol) is placed in 50 mL round-bottomed flasks, and 20mL CH is added2Cl2?
24 h are stirred at room temperature, then 110.4 mg KPF6 It is added into and continues to stir 2 h, be on a rotary evaporator spin-dried for solvent, use
Appropriate CH2Cl2Solid is dissolved, is filtered into reagent bottle, is slowly added to 20 mL n-hexanes along bottle wall, makes to be layered, use diffusion method
Recrystallization, obtains yellow solid product.
(2) by 39.8 mg iridium dimer (R1For methyl), N- (2,6-dimethylphenyl) -1- (2-
(diphenylphosphanyl) phenyl) methanimine (39.3mg, 0.10 mmol) is placed in 50 mL round-bottomed flasks
In, 20mL CH is added2Cl224 h are stirred at room temperature, then 110.4 mg KPF6 It is added into and continues to stir 2 h, rotating
Solvent is spin-dried on evaporimeter, with appropriate CH2Cl2Solid is dissolved, filters into reagent bottle, is being slowly added to 20 mL just along bottle wall
Hexane makes to be layered, be recrystallized with diffusion method, obtains yellow solid product.
(3) by 39.8 mg iridium dimer (R1For methyl), N- (2,6-diisopropylphenyl) -1- (2-
(diphenylphosphanyl) phenyl) methanimine (45.0 mg, 0.10 mmol) be placed in 50 mL round bottoms burning
In bottle, 20mL CH is added2Cl224 h are stirred at room temperature, then 110.4 mg KPF6 It is added into and continues to stir 2 h, revolving
Turn to be spin-dried for solvent on evaporimeter, with appropriate CH2Cl2Solid is dissolved, filters into reagent bottle, is slowly added to 20 mL along bottle wall
N-hexane makes to be layered, be recrystallized with diffusion method, obtains yellow solid product.
(4) by 39.8 mg iridium dimer (R1For methyl), N-cyclohexyl-1- (2- (diphenylphosphanyl)
Phenyl) methanimine (37.1 mg, 0.10 mmol) is placed in 50 mL round-bottomed flasks, and 20 mL CH are added2Cl2
24 h are stirred at room temperature, then 110.4 mg KPF6 It is added into and continues to stir 2 h, be on a rotary evaporator spin-dried for solvent,
With appropriate CH2Cl2Solid is dissolved, is filtered into reagent bottle, is slowly added to 20 mL n-hexanes along bottle wall, makes to be layered, with diffusion
Method recrystallization, obtains yellow solid product.
(5) by 39.8 mg iridium dimer (R1For methyl), N-benzyl-1- (2- (diphenylphosphanyl)
Phenyl) methanimine (38.0 mg, 0.10 mmol) is placed in 50 mL round-bottomed flasks, and 20mL CH is added2Cl2
24 h are stirred at room temperature, then 110.4 mg KPF6 It is added into and continues to stir 2 h, be on a rotary evaporator spin-dried for solvent,
With appropriate CH2Cl2Solid is dissolved, is filtered into reagent bottle, is slowly added to 20 mL n-hexanes along bottle wall, makes to be layered, with diffusion
Method recrystallization, obtains yellow solid product.
(6) by 39.8 mg iridium dimer (R1For methyl), 1- (2- (diphenylphosphanyl) phenyl)-N-
Phenethylmethanimine (39.3 mg, 0.10 mmol) is placed in 50 mL round-bottomed flasks, and 20 mL are added
CH2Cl224 h are stirred at room temperature, then 110.4 mg KPF6 It is added into and continues to stir 2 h, it on a rotary evaporator will be molten
Agent is spin-dried for, with appropriate CH2Cl2Solid is dissolved, is filtered into reagent bottle, is slowly added to 20 mL n-hexanes along bottle wall, makes to be layered,
It is recrystallized with diffusion method, obtains yellow solid product.
(7) by 53.7 mg iridium dimer (R1For xenyl), N-cyclohexyl-1- (2-
(diphenylphosphanyl) phenyl) methanimine (37.1 mg, 0.10 mmol) be placed in 50 mL round bottoms burning
In bottle, 20 mL CH are added2Cl224 h are stirred at room temperature, then 110.4 mg KPF6 It is added into and continues to stir 2 h,
Solvent is spin-dried on Rotary Evaporators, with appropriate CH2Cl2Solid is dissolved, filters into reagent bottle, is slowly added to 20 along bottle wall
ML n-hexane makes to be layered, be recrystallized with diffusion method, obtains yellow solid product.
(8) by 53.7 mg iridium dimer (R1For xenyl), 1- (2- (diphenylphosphanyl) phenyl)-N-
Phenethylmethanimine (39.3 mg, 0.10 mmol) is placed in 50 mL round-bottomed flasks, and 20 mL are added
CH2Cl224 h are stirred at room temperature, then 110.4 mg KPF6 It is added into and continues to stir 2 h, it on a rotary evaporator will be molten
Agent is spin-dried for, with appropriate CH2Cl2Solid is dissolved, is filtered into reagent bottle, is slowly added to 20 mL n-hexanes along bottle wall, makes to be layered,
It is recrystallized with diffusion method, obtains yellow solid product.
Beneficial effect
A kind of organic metal iridium anticancer complex of the disclosure of the invention, also discloses preparation method, and experiment shows preparation
Complex 1-8 is inhibited to the growth of gland cancer mankind's alveolar substrate epithelial cell (A549), illustrates that complex 1-8 has
Good Anticancer Activity in vitro.Complex of iridium in the present invention can carry out the modification of substituent group in multiple positions, and anticancer is living
Property it is good, be new class potential anticancer drug.
Detailed description of the invention
Fig. 1 is the mono-crystalline structures of complex 4 prepared by the embodiment of the present invention 4.
Fig. 2 is the nucleus magnetic hydrogen spectrum of complex 1 prepared by the embodiment of the present invention 1.
Fig. 3 is the nucleus magnetic hydrogen spectrum of complex 2 prepared by the embodiment of the present invention 2.
Fig. 4 is the nucleus magnetic hydrogen spectrum of complex 3 prepared by the embodiment of the present invention 3.
Fig. 5 is the nucleus magnetic hydrogen spectrum of complex 4 prepared by the embodiment of the present invention 4.
Fig. 6 is the nucleus magnetic hydrogen spectrum of complex 5 prepared by the embodiment of the present invention 5.
Fig. 7 is the nucleus magnetic hydrogen spectrum of complex 6 prepared by the embodiment of the present invention 6.
Fig. 8 is the nucleus magnetic hydrogen spectrum of complex 7 prepared by the embodiment of the present invention 7.
Fig. 9 is the nucleus magnetic hydrogen spectrum of complex 8 prepared by the embodiment of the present invention 8.
Figure 10 is the phosphorus spectrum of complex 1 prepared by the embodiment of the present invention 1.
Figure 11 is the phosphorus spectrum of complex 2 prepared by the embodiment of the present invention 2.
Figure 12 is the phosphorus spectrum of complex 3 prepared by the embodiment of the present invention 3.
Figure 13 is the phosphorus spectrum of complex 4 prepared by the embodiment of the present invention 4.
Figure 14 is the phosphorus spectrum of complex 5 prepared by the embodiment of the present invention 5.
Figure 15 is the phosphorus spectrum of complex 6 prepared by the embodiment of the present invention 6.
Figure 16 is the phosphorus spectrum of complex 7 prepared by the embodiment of the present invention 7.
Figure 17 is the phosphorus spectrum of complex 8 prepared by the embodiment of the present invention 8.
Figure 18 is the mass spectrum of complex 1 prepared by the embodiment of the present invention 1.
Figure 19 is the mass spectrum of complex 2 prepared by the embodiment of the present invention 2.
Figure 20 is the mass spectrum of complex 3 prepared by the embodiment of the present invention 3.
Figure 21 is the mass spectrum of complex 4 prepared by the embodiment of the present invention 4.
Figure 22 is the mass spectrum of complex 5 prepared by the embodiment of the present invention 5.
Figure 23 is the mass spectrum of complex 6 prepared by the embodiment of the present invention 6.
Figure 24 is the mass spectrum of complex 7 prepared by the embodiment of the present invention 7.
Figure 25 is the mass spectrum of complex 8 prepared by the embodiment of the present invention 8.
Specific embodiment
It elaborates below to the embodiment of the present invention, the present embodiment carries out under the premise of the technical scheme of the present invention
Implement, the detailed implementation method and specific operation process are given, but protection scope of the present invention is not limited to following implementation
Example.
Embodiment 1
By 39.8 mg iridium dimer (R1For methyl), 1- (2- (diphenylphosphanyl) phenyl)-N-
Phenylmethanimine (36.5 mg, 0.10 mmol) is placed in 50 mL round-bottomed flasks, and 20mL CH is added2Cl2?
24 h are stirred at room temperature, then 110.4 mg KPF6 It is added into and continues to stir 2 h, be on a rotary evaporator spin-dried for solvent, use
Appropriate CH2Cl2Solid is dissolved, is filtered into reagent bottle, is slowly added to 20 mL n-hexanes along bottle wall, makes to be layered, use diffusion method
Recrystallization, obtains 47 mg of yellow solid product (yield, 54 %).1H NMR (500 MHz, DMSO) δ 8.62 (d, J
= 2.4 Hz, 1H, HC=N), 7.87-7.80 (m, 3H, aryl-H), 7.72 (ddt, J = 18.3, 15.9,
7.8 Hz, 11H, aryl-H), 7.62 (t, J=7.6 Hz, 1H, aryl-H), 7.49 (dd, J = 10.6,
7.8 Hz, 1H, aryl-H), 7.41 (t, J=7.5 Hz, 1H, aryl-H), 7.12 (d, J = 7.7 Hz,
2H, aryl-H), 1.02 (d, J = 2.3 Hz, 15H, Cp*-H). 31P NMR (202 MHz, DMSO) δ 11.41
(P(Ph)2), -133.65 (PF6), -137.17 (PF6), -140.68 (PF6), -144.19 (PF6), -147.71
(PF6), -151.22 (PF6), -154.73 (PF6). MALDI-TOF-MS (m/z): C35H35ClIrPN: theoretical value:
728.1825 actually measured 728.1370 [M-PF6]+.
Embodiment 2
By 39.8 mg iridium dimer (R1For methyl), N- (2,6-dimethylphenyl) -1- (2-
(diphenylphosphanyl) phenyl) methanimine (39.3 mg, 0.10 mmol) be placed in 50 mL round bottoms burning
In bottle, 20mL CH is added2Cl224 h are stirred at room temperature, then 110.4 mg KPF6 It is added into and continues to stir 2 h, revolving
Turn to be spin-dried for solvent on evaporimeter, with appropriate CH2Cl2Solid is dissolved, filters into reagent bottle, is slowly added to 20 mL along bottle wall
N-hexane makes to be layered, be recrystallized with diffusion method, obtains 63 mg of yellow solid product (yield, 70 %).1H NMR (500
MHz, CDCl3) δ 8.07 (d, J = 3.2 Hz, 1H, HC=N), 7.72-7.65 (m, 4H, aryl-H),
7.64-7.58 (m, 5H, aryl-H), 7.54 (td, J=8.0,2.8 Hz, 2H, aryl-H), 7.28 (d,
J=3.8 Hz, 1H, aryl-H), 7.23 (s, 1H, aryl-H), 7.18 (d, J=6.9 Hz, 1H, aryl-H), 7.07-7.00 (m, 3H, aryl-H), 2.27 (s, 3H, o-aniline-CH 3), 1.37 (s, 3H, o-
aniline-CH 3), 1.16 (d, J = 2.4 Hz, 15H, Cp*-H). 31P NMR (202 MHz, CDCl3) δ 6.64
(P(Ph)2), -133.94 (PF6), -137.46 (PF6), -140.98 (PF6), -144.50 (PF6), -148.02
(PF6), -151.53 (PF6), -155.05 (PF6). MALDI-TOF-MS (m/z): C37H39ClIrPN: theoretical value:
756.2138 actually measured 756.1720 [M-PF6]+.
Embodiment 3
By 39.8 mg iridium dimer (R1For methyl), N- (2,6-diisopropylphenyl) -1- (2-
(diphenylphosphanyl) phenyl) methanimine (45.0 mg, 0.10 mmol) be placed in 50 mL round bottoms burning
In bottle, 20mL CH is added2Cl224 h are stirred at room temperature, then 110.4 mg KPF6 It is added into and continues to stir 2 h, revolving
Turn to be spin-dried for solvent on evaporimeter, with appropriate CH2Cl2Solid is dissolved, filters into reagent bottle, is slowly added to 20 mL along bottle wall
N-hexane makes to be layered, be recrystallized with diffusion method, obtains 44 mg of yellow solid product (yield, 46 %).1H NMR (500
MHz, CDCl3) δ 8.07 (d, J = 2.9 Hz, 1H, HC=N), 7.68 (tt, J = 14.9, 7.4 Hz, 5H,
Aryl-H), 7.63-7.59 (m, 1H, aryl-H), 7.51 (dd, J=6.7,4.6 Hz, 4H, aryl-H),
7.34-7.27 (m, 3H, aryl-H), 7.24 (d, J=7.8 Hz, 2H, aryl-H), 7.16 – 7.03
(m, 2H, aryl-H), 3.46 – 3.43 (m, 1H, i Pr-CH), 2.19 – 2.12 (m, 1H, i Pr-CH),
1.38 (d, J = 6.8 Hz, 3H, i Pr-CH 3), 1.19 (d, J = 2.4 Hz, 15H, Cp*-H), 1.10 (d,J = 6.6 Hz, 3H, i Pr-CH 3), 1.06 (d, J = 6.7 Hz, 3H, i Pr-CH 3), 0.18 (d, J = 6.6
Hz, 3H, i Pr-CH 3). 31P NMR (202 MHz, CDCl3) δ 6.89 (P(Ph)2), -133.94 (PF6), -
137.46 (PF6), -140.98 (PF6), -144.50 (PF6), -148.02 (PF6), -151.54 (PF6),
155.06 (PF6). MALDI-TOF-MS (m/z): C41H47ClIrPN: theoretical value: 812.2764, it is actually measured
812.1550 [M-PF6]+.
Embodiment 4
By 39.8 mg iridium dimer (R1For methyl), N-cyclohexyl-1- (2- (diphenylphosphanyl) phenyl)
Methanimine (37.1 mg, 0.10 mmol) is placed in 50 mL round-bottomed flasks, and 20 mL CH are added2Cl2In room temperature
24 h of lower stirring, then 110.4 mg KPF6 It is added into and continues to stir 2 h, be on a rotary evaporator spin-dried for solvent, with appropriate
CH2Cl2Solid is dissolved, is filtered into reagent bottle, is slowly added to 20 mL n-hexanes along bottle wall, makes to be layered, tied again with diffusion method
Crystalline substance obtains 58 mg of yellow solid product (yield, 66 %).1H NMR (500 MHz, DMSO) δ 8.64 (d, J =
2.5 Hz, 1H, HC=N), 7.82 (dd, J=7.3,3.8 Hz, 1H, aryl-H), 7.75 – 7.53 (m,
12H, aryl-H), 7.46 (dd, J=10.0,8.0 Hz, 1H, aryl-H), 4.03 (t, J = 11.8 Hz,
1H, Cy-H), 1.95 (t, J = 11.7 Hz, 2H, Cy-H), 1.84 (d, J = 13.3 Hz, 1H, Cy-H),
1.75 (t, J = 12.2 Hz, 2H, Cy-H), 1.68 (d, J = 12.5 Hz, 1H, Cy-H), 1.63 – 1.53
(m, 1H, Cy-H), 1.53 – 1.47 (m, 1H, Cy-H), 1.44 (d, J = 14.1 Hz, 1H, Cy-H),
1.40 (d, J = 2.1 Hz, 15H, Cp*-H), 1.23 (dd, J = 25.8, 12.8 Hz, 1H, Cy-H). 31P
NMR (202 MHz, DMSO) δ 12.32 (P(Ph)2), -137.17 (PF6), -140.68 (PF6), -144.19
(PF6), -147.71 (PF6), -151.22 (PF6), -154.73 (PF6). MALDI-TOF-MS (m/z):
C35H41ClIrPN: theoretical value: 734.2294, actually measured 734.1700 [M-PF6]+.
Embodiment 5
By 39.8 mg iridium dimer (R1For methyl), N-benzyl-1- (2- (diphenylphosphanyl) phenyl)
Methanimine (38.0 mg, 0.10 mmol) is placed in 50 mL round-bottomed flasks, and 20mL CH is added2Cl2At room temperature
24 h are stirred, then 110.4 mg KPF6 It is added into and continues to stir 2 h, be on a rotary evaporator spin-dried for solvent, with appropriate
CH2Cl2Solid is dissolved, is filtered into reagent bottle, is slowly added to 20 mL n-hexanes along bottle wall, makes to be layered, tied again with diffusion method
Crystalline substance obtains 53 mg of yellow solid product (yield, 60 %).1H NMR (500 MHz, CDCl3) δ 8.11 (d, J =
1.7 Hz, 1H, HC=N), 7.63 (dd, J=13.1,7.3 Hz, 6H, aryl-H), 7.59 – 7.48 (m,
6H, aryl-H), 7.42 (td, J=7.8,2.7 Hz, 2H, aryl-H), 7.30-7.27 (m, 3H, virtues
Base-H), 7.21-7.16 (m, 2H, aryl-H), 5.43 (d, J = 15.4 Hz, 1H, ArCH 2N), 5.30
(d, J = 15.4 Hz, 1H, ArCH 2N), 1.41 (s, 15H, Cp*-H). 31P NMR (202 MHz, CDCl3) δ
8.02 (P(Ph)2), -133.70 (PF6), -137.22 (PF6), -140.74 (PF6), -144.26 (PF6), -
147.78 (PF6), -151.30 (PF6), -154.82 (PF6). MALDI-TOF-MS (m/z): C36H37ClIrPN:
Theoretical value: 742.1981, actually measured 742.1977 [M-PF6]+.
Embodiment 6
By 39.8 mg iridium dimer (R1For methyl), 1- (2- (diphenylphosphanyl) phenyl)-N-
Phenethylmethanimine (39.3 mg, 0.10 mmol) is placed in 50 mL round-bottomed flasks, and 20 mL are added
CH2Cl224 h are stirred at room temperature, then 110.4 mg KPF6 It is added into and continues to stir 2 h, it on a rotary evaporator will be molten
Agent is spin-dried for, with appropriate CH2Cl2Solid is dissolved, is filtered into reagent bottle, is slowly added to 20 mL n-hexanes along bottle wall, makes to be layered,
It is recrystallized with diffusion method, obtains 70 mg of yellow solid product (yield, 78 %).1H NMR (500 MHz, DMSO) δ
8.29 (d, J = 1.8 Hz, 1H, HC=N), 7.76 (t, J=7.6 Hz, 1H, aryl-H), 7.73 – 7.61
(m, 6H, aryl-H), 7.57 (dt, J=8.9,3.5 Hz, 6H, aryl-H), 7.48 (dd, J = 7.3,
3.7 Hz, 1H, aryl-H), 7.29 (dd, J=11.1,4.4 Hz, 2H, aryl-H), 7.24 (dd, J =
6.2,3.9 Hz, 1H, aryl-H), 7.23-7.17 (m, 2H, aryl-H), 4.53 – 4.41 (m, 1H,
ArCH2CH 2N), 4.28 – 4.17 (m, 1H, ArCH2CH 2N), 2.71 (ddd, J = 13.4, 8.3, 5.0 Hz,
1H, ArCH 2CH2N), 2.58 (dt, J = 13.7, 8.1 Hz, 1H, ArCH 2CH2N), 1.38 (s, 15H, Cp*-H). 31P NMR (202 MHz, DMSO) δ 8.09 (P(Ph)2), -133.65 (PF6), -137.16 (PF6), -
140.68 (PF6), -144.19 (PF6), -147.70 (PF6), -151.22 (PF6), -154.73 (PF6).
MALDI-TOF-MS (m/z): C37H39ClIrPN: theoretical value: 756.2138, actually measured 756.2055 [M-PF6]+.
Embodiment 7
By 53.7 mg iridium dimer (R1For xenyl), N-cyclohexyl-1- (2- (diphenylphosphanyl)
Phenyl) methanimine (37.1 mg, 0.10 mmol) is placed in 50 mL round-bottomed flasks, and 20 mL CH are added2Cl2
24 h are stirred at room temperature, then 110.4 mg KPF6 It is added into and continues to stir 2 h, be on a rotary evaporator spin-dried for solvent,
With appropriate CH2Cl2Solid is dissolved, is filtered into reagent bottle, is slowly added to 20 mL n-hexanes along bottle wall, makes to be layered, with diffusion
Method recrystallization, obtains 63 mg of yellow solid product (yield, 62 %).1H NMR (500 MHz, DMSO) δ 8.61 (s,
1H, HC=N), 7.85-7.80 (m, 3H, aryl-H), 7.75-7.70 (m, 5H, aryl-H), 7.69 –
7.60 (m, 11H, aryl-H), 7.54-7.49 (m, 3H, aryl-H), 7.43 (t, J = 7.4 Hz, 1H,
Aryl-H), 3.66 (t, J = 11.7 Hz, 1H, Cy-H), 2.23 (s, 3H, Cpxbiph-CH 3), 1.98 (d, J
= 11.7 Hz, 1H, Cy-H), 1.68 (s, 2H, Cy-H), 1.66 – 1.57 (m, 4H, Cy-H and Cpxbiph-
CH 3), 1.54 (d, J = 1.7 Hz, 3H, Cpxbiph-CH 3), 1.45 (dt, J = 21.1, 7.3 Hz, 1H,
Cy-H), 1.30 (d, J = 10.7 Hz, 2H, Cy-H), 1.03 – 0.93 (m, 2H, Cy-H), 0.30 (s,
3H, Cpxbiph-CH 3), -0.13 (dt, J = 22.1, 11.0 Hz, 1H, Cy-H). 31P NMR (202 MHz,
DMSO) δ 12.29 (P(Ph)2), -133.65 (PF6), -137.16 (PF6), -140.68 (PF6), -144.19
(PF6), -147.70 (PF6), -151.22 (PF6), -154.73 (PF6). MALDI-TOF-MS (m/z):
C46H47ClIrPN: theoretical value: 872.2764, actually measured 872.2042 [M-PF6]+.
Embodiment 8
By 53.7 mg iridium dimer (R1For xenyl), 1- (2- (diphenylphosphanyl) phenyl)-N-
Phenethylmethanimine (39.3 mg, 0.10 mmol) is placed in 50 mL round-bottomed flasks, and 20 mL are added
CH2Cl224 h are stirred at room temperature, then 110.4 mg KPF6 It is added into and continues to stir 2 h, it on a rotary evaporator will be molten
Agent is spin-dried for, with appropriate CH2Cl2Solid is dissolved, is filtered into reagent bottle, is slowly added to 20 mL n-hexanes along bottle wall, makes to be layered,
It is recrystallized with diffusion method, obtains 53 mg of yellow solid product (yield, 51 %).1H NMR (500 MHz, DMSO) δ
8.79 (d, J = 1.9 Hz, 1H, HC=N), 7.94-7.70 (m, 9H, aryl-H), 7.65 – 7.29 (m,
14H, aryl-H), 7.24-7.11 (m, 3H, aryl-H), 6.96-6.88 (m, 2H, aryl-H), 4.30
(td, J = 11.6, 5.8 Hz, 1H, ArCH2CH 2N), 4.13 (td, J = 11.6, 4.8 Hz, 1H,
ArCH2CH 2N), 3.20 (td, J = 12.0, 5.2 Hz, 1H, ArCH 2CH2N), 2.43 (td, J = 12.0,
4.2 Hz, 1H, ArCH 2CH2N), 1.93 (d, J = 1.7 Hz, 3H, Cpxbiph-CH 3), 1.70 (d, J = 3.9
Hz, 3H, Cpxbiph-CH 3), 1.49 (d, J = 3.0 Hz, 3H, Cpxbiph-CH 3), 0.53 (s, 3H, Cpxbiph-
CH 3). 31P NMR (202 MHz, DMSO) δ 7.08 (P(Ph)2), -133.66 (PF6), -137.17 (PF6), -
140.68 (PF6), -144.20 (PF6), -147.71 (PF6`), -151.22 (PF6), -154.73 (PF6).
MALDI-TOF-MS (m/z): C48H45ClIrPN: theoretical value: 894.2607, actually measured 894.2693 [M-PF6]+.
Embodiment 9
Complex 1-8 with anticancer activity tests the proliferation inhibition activity of tumor cell line:
(1) preparation of untested compound: solid complexes are dissolved in DMSO, are made into certain density stock solution, are used cell
Culture solution further dilutes stock solution until reaching working concentration, cultivates 24 h；
(2) cell growth inhibition test (mtt assay):
1) 5000 gland cancer mankind's alveolar substrate epithelial cells (A549) are taken, cell suspension is configured to, is inoculated in 96 well culture plates
In；
2) with no medicine culture medium pre-cultured cell, 5%CO2, 310K be incubated for 24 hours, prepared untested compound is added, train
Support 24 h；
3) the MTT solution of 15 μ L, 5 mg/mL is added in every hole, continues culture 4 hours, forms purple crystal substance first a ceremonial jade-ladle, used in libation；
4) culture is terminated, culture solution in hole is carefully sucked, the DMSO that 100 μ L are added in every hole sufficiently dissolves first a ceremonial jade-ladle, used in libation precipitating, oscillator
After mixing, the microplate reader OD value that wavelength is that 570nm measures each hole；
5) each to test in triplicate, IC50 =average value ± SEM
The inhibiting rate that complex 1-8 and cis-platinum grow gland cancer mankind's alveolar substrate epithelial cell (A549) is shown in Table 1.
Table 1
By embodiment 9 as can be seen that complex 1 ~ 8 shows extraordinary anticancer activity, far superior to it has been commercialized
The activity of cis-platinum.In addition, the modification of substituent group influences less the anticancer activity of complex on phosphinimine ligand.
Obviously, various changes and modifications can be made to the invention without departing from essence of the invention by those skilled in the art
Mind and range.In this way, if these modifications and changes of the present invention belongs to the range of the claims in the present invention and its equivalent technologies
Within, then the present invention is also intended to include these modifications and variations.
Claims (7)
1. a kind of iridium anticancer complex containing two tooth cheland of phosphinimine, which is characterized in that its structural formula such as formula (I) institute
Show:
；
In formula (I), R1For hydrogen, aryl, alkyl, naphthenic base, halogen；R2、R3It is independently of one another naphthenic base or C7~C30Substitution
Aryl；R4For C1~C15Alkyl or C6~C30Aryl；X is Cl-、PF6 -、BF4 -、BPh4 -、SbF6 -、、Or。
2. the iridium anticancer complex containing two tooth cheland of phosphinimine according to claim 1, it is characterised in that institute
It states in formula (I), the substituent group on the aryl is C1~C12Alkyl.
3. the iridium anticancer complex according to claim 1 containing two tooth cheland of phosphinimine, which is characterized in that formula
(I) particular compound structure are as follows:
。
4. a kind of preparation of the described in any item iridium anticancer complexes containing two tooth cheland of phosphinimine of claims 1 to 3
Method, which is characterized in that use following steps:
；
Reaction forms the ring penta containing substituent group under the conditions of iridium dimer, two tooth ligand of P^N and AX are added in methylene chloride
The hexa-coordinate complex of iridium of diene ring, two tooth cheland of P^N and chlorine atom and metal iridium coordination；The AX be NaX,
KX, AgX or NH4X。
5. the preparation method according to claim 4: it is characterized in that, when the complex is 1-8, specific steps are as follows:
Complex 1: by R in 39.8 mg formulas (II)1Iridium dimer, 36.5mg 1- (2- for methyl
(diphenylphosphanyl) phenyl)-N-phenylmethanimine is placed in 50 mL round-bottomed flasks, 20mL is added
CH2Cl224 h are stirred at room temperature, then 110.4 mg KPF6 It is added into and continues to stir 2 h, it on a rotary evaporator will be molten
Agent is spin-dried for, with appropriate CH2Cl2Solid is dissolved, is filtered into reagent bottle, is slowly added to 20 mL n-hexanes along bottle wall, makes to be layered,
It is recrystallized with diffusion method, obtains yellow solid product；
Complex 2: by R in 39.8 mg formulas (II)1Iridium dimer, 39.3mg N- (2,6- for methyl
Dimethylphenyl) -1- (2- (diphenylphosphanyl) phenyl) methanimine is placed in 50 mL round-bottomed flasks
In, 20mL CH is added2Cl224 h are stirred at room temperature, then 110.4 mg KPF6 It is added into and continues to stir 2 h, rotating
Solvent is spin-dried on evaporimeter, with appropriate CH2Cl2Solid is dissolved, filters into reagent bottle, is being slowly added to 20 mL just along bottle wall
Hexane makes to be layered, be recrystallized with diffusion method, obtains yellow solid product；
Complex 3: by R in 39.8 mg formulas (II)1Iridium dimer, 45.0mg N- (2,6- for methyl
Diisopropylphenyl) -1- (2- (diphenylphosphanyl) phenyl) methanimine is placed in 50 mL round bottoms
In flask, 20mL CH is added2Cl224 h are stirred at room temperature, then 110.4 mg KPF6 It is added into and continues to stir 2 h,
Solvent is spin-dried on Rotary Evaporators, with appropriate CH2Cl2Solid is dissolved, filters into reagent bottle, is slowly added to 20 along bottle wall
ML n-hexane makes to be layered, be recrystallized with diffusion method, obtains yellow solid product；
Complex 4: by R in 39.8 mg formulas (II)1Iridium dimer, 37.1mg N-cyclohexyl-1- (2- for methyl
(diphenylphosphanyl) phenyl) methanimine is placed in 50 mL round-bottomed flasks, 20 mL CH are added2Cl2?
24 h are stirred at room temperature, then 110.4 mg KPF6 It is added into and continues to stir 2 h, be on a rotary evaporator spin-dried for solvent, use
Appropriate CH2Cl2Solid is dissolved, is filtered into reagent bottle, is slowly added to 20 mL n-hexanes along bottle wall, makes to be layered, use diffusion method
Recrystallization, obtains yellow solid product；
Complex 5: by R in 39.8 mg formulas (II)1Iridium dimer, 38.0mg N-benzyl-1- (2- for methyl
(diphenylphosphanyl) phenyl) methanimine is placed in 50 mL round-bottomed flasks, 20mL CH is added2Cl2?
24 h are stirred at room temperature, then 110.4 mg KPF6 It is added into and continues to stir 2 h, be on a rotary evaporator spin-dried for solvent, use
Appropriate CH2Cl2Solid is dissolved, is filtered into reagent bottle, is slowly added to 20 mL n-hexanes along bottle wall, makes to be layered, use diffusion method
Recrystallization, obtains yellow solid product；
Complex 6: by R in 39.8 mg formulas (II)1Iridium dimer, 39.3mg 1- (2- for methyl
(diphenylphosphanyl) phenyl)-N-phenethylmethanimine is placed in 50 mL round-bottomed flasks, it is added 20
mL CH2Cl224 h are stirred at room temperature, then 110.4 mg KPF6 It is added into and continues to stir 2 h, on a rotary evaporator
Solvent is spin-dried for, with appropriate CH2Cl2Solid is dissolved, is filtered into reagent bottle, is slowly added to 20 mL n-hexanes along bottle wall, makes
Layering, is recrystallized with diffusion method, obtains yellow solid product；
Complex 7: by R in 53.7 mg formulas (II)1Iridium dimer, 37.1mg N-cyclohexyl-1- (2- for xenyl
(diphenylphosphanyl) phenyl) methanimine is placed in 50 mL round-bottomed flasks, 20 mL CH are added2Cl2?
24 h are stirred at room temperature, then 110.4 mg KPF6 It is added into and continues to stir 2 h, be on a rotary evaporator spin-dried for solvent, use
Appropriate CH2Cl2Solid is dissolved, is filtered into reagent bottle, is slowly added to 20 mL n-hexanes along bottle wall, makes to be layered, use diffusion method
Recrystallization, obtains yellow solid product；
Complex 8: by R in 53.7 mg formulas (II)1Iridium dimer, 39.3mg 1- (2- for xenyl
(diphenylphosphanyl) phenyl)-N-phenethylmethanimine is placed in 50 mL round-bottomed flasks, it is added 20
mL CH2Cl224 h are stirred at room temperature, then 110.4 mg KPF6 It is added into and continues to stir 2 h, on a rotary evaporator
Solvent is spin-dried for, with appropriate CH2Cl2Solid is dissolved, is filtered into reagent bottle, is slowly added to 20 mL n-hexanes along bottle wall, makes
Layering, is recrystallized with diffusion method, obtains yellow solid product.
6. the iridium anticancer complex containing two tooth cheland of phosphinimine described in a kind of one of claim 1-5 is in preparation anticancer
Application in drug.
7. the iridium anticancer complex containing two tooth cheland of phosphinimine described in a kind of one of claim 1-5 is preparing anti-gland
Application in cancer drug.
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